The role of anaphylatoxins, C3a and C5a, in inflammation will be explored in three related areas to obtain data relevant to the causation of lung diseases such as OIDS, ARDS and asthma. I will first test the hypothesis that repeated exposure of lungs to these humoral factors results in injury similar to that observed in various chronic lung diseases. Recent evident suggests that this is true and the hypothesis will be tested by repeatedly administering the factors C3a and C5a both intravenously and intrabronchially to guinea pigs. Second, the reactivity of cardiac tissue with anaphylatoxins will be investigated; this is an area virtually unexplored to date. Specifically, two approaches offer a potential for discerning clinically relevant results: 1) the in vivo acute pathohistologic responses will be obtained and 2) the pharmacology of anaphylatoxin/cardiac tissue interactions will be recorded. Third, the fundamental cellular basis of inflammation mediated by C3a and C5a will be studied by characterizing interactions of C3a and C5a with various cell types directly involved in the inflammatory response. This experimentation focuses on the central issue of importance, namely mechanisms operating at the cellular level. We can only truly understand phenomena manifested at the organism or tissue level by defining cellular interactions. The scarcity of purified C3a and C5a is a major difficulty posed in studying these mediator-cell interactions. My plan is to produce mg quantities of the humoral factors from both human and porcine sources for these studies.